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Trial record 4 of 10 for:    "Clear Cell Renal Cell Carcinoma" | "Interferon alpha-2"

A Study of Avastin (Bevacizumab) Added to Interferon Alfa-2a (Roferon) Therapy in Patients With Metastatic Renal Cell Cancer With Nephrectomy

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ClinicalTrials.gov Identifier: NCT00738530
Recruitment Status : Completed
First Posted : August 20, 2008
Results First Posted : June 23, 2016
Last Update Posted : June 23, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Renal Cell Cancer
Interventions Drug: Bevacizumab [Avastin]
Drug: Interferon alfa 2a [Roferon]
Drug: Placebo
Enrollment 649
Recruitment Details A total of 821 participants were screened for this study, and 649 of these were randomized to receive double-blind treatment.
Pre-assignment Details  
Arm/Group Title Bevacizumab + IFN-Alfa-2A Placebo + IFN-Alfa-2A
Hide Arm/Group Description Bevacizumab infusions were administered every 2 weeks at a dose of 10 milligram per kilogram (mg/kg) for 52 weeks or until disease progression or unacceptable toxicity. Interferon alfa-2a (IFN-Alfa-2A) was administered 3 times per week as a subcutaneous injection at a dose of 9 million international units (MIU) for 52 weeks or until disease progression or major toxicity. Placebo matched with Bevacizumab infusions were administered every 2 weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Period Title: Overall Study
Started 327 322
Treated 325 316
Completed 93 84
Not Completed 234 238
Reason Not Completed
Death             220             224
Lost to Follow-up             8             6
Withdrawal by Subject             6             8
Arm/Group Title Bevacizumab + IFN-Alfa-2A Placebo + IFN-Alfa-2A Total
Hide Arm/Group Description Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity. Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity. Total of all reporting groups
Overall Number of Baseline Participants 327 322 649
Hide Baseline Analysis Population Description
Intent-to-treat population (ITT) included all participants randomized into the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 327 participants 322 participants 649 participants
60.1  (10.12) 59.4  (10.89) 59.7  (10.51)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 327 participants 322 participants 649 participants
Female
105
  32.1%
87
  27.0%
192
  29.6%
Male
222
  67.9%
235
  73.0%
457
  70.4%
1.Primary Outcome
Title Percentage of Participants Who Died
Hide Description [Not Specified]
Time Frame Baseline up to 4.25 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized into the study.
Arm/Group Title Bevacizumab + IFN-Alfa-2A Placebo + IFN-Alfa-2A
Hide Arm/Group Description:
Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Overall Number of Participants Analyzed 327 322
Measure Type: Number
Unit of Measure: percentage of participants
67.3 69.6
2.Primary Outcome
Title Overall Survival (OS) Duration
Hide Description Duration of survival was defined as the time between the date of randomization and date of death due to any cause. Participants still alive at the time of analysis were censored at the date they were last known to be alive. Kaplan-Meier estimates were used for analysis.
Time Frame Baseline until death (up to 4.25 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized into the study.
Arm/Group Title Bevacizumab + IFN-Alfa-2A Placebo + IFN-Alfa-2A
Hide Arm/Group Description:
Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Overall Number of Participants Analyzed 327 322
Median (95% Confidence Interval)
Unit of Measure: months
23.3
(20.4 to 27.0)
21.3
(18.4 to 24.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab + IFN-Alfa-2A, Placebo + IFN-Alfa-2A
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3360
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.76 to 1.10
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Disease Progression or Death
Hide Description Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.
Time Frame Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized into the study.
Arm/Group Title Bevacizumab + IFN-Alfa-2A Placebo + IFN-Alfa-2A
Hide Arm/Group Description:
Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Overall Number of Participants Analyzed 327 322
Measure Type: Number
Unit of Measure: percentage of participants
92.0 92.5
4.Secondary Outcome
Title Progression Free Survival (PFS) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Hide Description Progression-free survival was defined as the time between the date of randomization and the first date of documented progression or date of death due to any cause, whichever occurred first. Tumor assessment was performed using modified RECIST. Progressive disease was defined as at least a 20 percentage(%) increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants without an event were censored at the date of last follow-up for progression or date of last available tumor measurement if no follow-up assessment for progression was performed. Participants who were randomized but not exposed to study drug and had no further follow-up were censored on the day of randomization.
Time Frame Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized into the study.
Arm/Group Title Bevacizumab + IFN-Alfa-2A Placebo + IFN-Alfa-2A
Hide Arm/Group Description:
Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Overall Number of Participants Analyzed 327 322
Median (95% Confidence Interval)
Unit of Measure: months
10.2
(7.7 to 11.1)
5.5
(4.2 to 5.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab + IFN-Alfa-2A, Placebo + IFN-Alfa-2A
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.64 to 0.88
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Time to Progression (TTP) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Hide Description Time to progression was defined as the time between date of randomization and date of documented progression. Tumor assessment was performed using mRECIST. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants without an event (including participants who died before progressive disease) were censored at the date of last follow-up for progression or date of last available tumor measurement if no follow-up assessment for progression was performed. Participants who were randomized but not exposed to study drug and had no further follow-up were censored on the day of randomization.
Time Frame Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized into the study.
Arm/Group Title Bevacizumab + IFN-Alfa-2A Placebo + IFN-Alfa-2A
Hide Arm/Group Description:
Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Overall Number of Participants Analyzed 327 322
Median (95% Confidence Interval)
Unit of Measure: months
10.2
(7.9 to 11.6)
5.5
(4.3 to 5.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab + IFN-Alfa-2A, Placebo + IFN-Alfa-2A
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.62 to 0.86
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With Treatment Failure
Hide Description Treatment failure is defined as insufficient therapeutic response (including disease progression), death, withdrawal of treatment due to adverse events or laboratory abnormality, or withdrawal of informed consent. Tumor assessment was performed using mRECIST. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.
Time Frame Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized into the study.
Arm/Group Title Bevacizumab + IFN-Alfa-2A Placebo + IFN-Alfa-2A
Hide Arm/Group Description:
Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Overall Number of Participants Analyzed 327 322
Measure Type: Number
Unit of Measure: percentage of participants
90.5 91.6
7.Secondary Outcome
Title Time to Treatment Failure (TTF) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Hide Description Time to treatment failure was defined as the time between the date of randomization and the date of insufficient therapeutic response (including disease progression), death, withdrawal of treatment due to adverse events or laboratory abnormality, or withdrawal of informed consent. Tumor assessment was performed using mRECIST. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants without an event were censored at the date of last tumor assessment or last treatment administration, whichever occurred last. Participants who were randomized but not exposed to study drug and had no further follow-up were censored on the day of randomization.
Time Frame Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized into the study.
Arm/Group Title Bevacizumab + IFN-Alfa-2A Placebo + IFN-Alfa-2A
Hide Arm/Group Description:
Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Overall Number of Participants Analyzed 327 322
Median (95% Confidence Interval)
Unit of Measure: months
8.1
(7.1 to 10.2)
4.5
(3.8 to 5.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab + IFN-Alfa-2A, Placebo + IFN-Alfa-2A
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0023
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.66 to 0.92
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants With Objective Response According to mRECIST
Hide Description Objective response referred to participants with complete response (CR) or partial response (PR). CR: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR: greater than or equal to (>=) 30% decrease in sum of the longest diameter (LD) of all target lesions taking as reference the screening sum LD. To be assigned a status of PR or CR, changes in tumor measurements had to be confirmed by repeat assessments that should have been performed no less than 4 weeks after the criteria for response were first met. Longer intervals as determined by the study protocol were also appropriate.
Time Frame Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized into the study. Number of participants analyzed (N) = participants with measurable disease at baseline.
Arm/Group Title Bevacizumab + IFN-Alfa-2A Placebo + IFN-Alfa-2A
Hide Arm/Group Description:
Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Overall Number of Participants Analyzed 306 289
Measure Type: Number
Unit of Measure: percentage of participants
32.4 12.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab + IFN-Alfa-2A, Placebo + IFN-Alfa-2A
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value 19.90
Confidence Interval (2-Sided) 95%
13.2 to 26.6
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percentage of Participants With Best Overall Response According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Hide Description Best response recorded from the start of treatment until disease progression. Based on assessment of CR, PR, stable disease (SD), or progressive disease (PD), according to mRECIST. CR: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR: >=30% decrease under baseline of the sum of the LD of all target lesions. CR and PR persist on repeat imaging study at least 4 weeks after initial documentation. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Reference is the smallest sum LD. PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.
Time Frame Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants randomized into the study. Number of participants analyzed (N) = participants with measurable disease at baseline.
Arm/Group Title Bevacizumab + IFN-Alfa-2A Placebo + IFN-Alfa-2A
Hide Arm/Group Description:
Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Overall Number of Participants Analyzed 306 289
Measure Type: Number
Unit of Measure: percentage of participants
Complete Response (CR) 1.6 2.4
Partial Response (PR) 30.7 10.0
Stable Disease (SD) 44.4 50.5
Progressive Disease (PD) 20.6 33.2
Missing (no response assessment) 2.6 3.8
10.Secondary Outcome
Title Change From Baseline in Karnofsky Performance Status
Hide Description Karnofsky performance score is used to quantify participant’s general well-being and activities of daily life and participants were classified based on their functional impairment. Karnofsky performance score is 11 level score which ranges between 0 (death) to 100 (no evidence of disease). Higher score means higher ability to perform daily tasks.
Time Frame Baseline, Week 7, 15, 23, 31, 43
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: all participants randomized and exposed to study drug (8 randomized participants did not receive study treatment and were not included, 2 in bevacizumab and 6 in placebo group). 12 participants randomized to placebo received bevacizumab, were included in bevacizumab arm. n=number of evaluable participants at specified time point.
Arm/Group Title Bevacizumab + IFN-Alfa-2A Placebo + IFN-Alfa-2A
Hide Arm/Group Description:
Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
Overall Number of Participants Analyzed 337 304
Median (Full Range)
Unit of Measure: score on a scale
Baseline (n=337, 304)
90
(70 to 100)
90
(70 to 100)
Change at Week 7 (n=291, 263)
0
(-50 to 10)
0
(-60 to 20)
Change at Week 15 (n=242, 196)
0
(-40 to 20)
0
(-60 to 20)
Change at Week 23 (n=195, 143)
0
(-90 to 20)
0
(-60 to 20)
Change at Week 31 (n=166, 108)
0
(-40 to 20)
0
(-50 to 20)
Change at Week 43 (n=137, 79)
0
(-40 to 20)
0
(-20 to 10)
Time Frame Baseline up to 4.25 years
Adverse Event Reporting Description Safety population: all participants randomized and exposed to study drug (8 randomized participants did not receive study treatment and were not included, 2 in bevacizumab and 6 in placebo group). 12 participants randomized to placebo received bevacizumab, were included in bevacizumab arm. n=number of evaluable participants at specified time point.
 
Arm/Group Title Bevacizumab + IFN-Alfa-2A Placebo + IFN-Alfa-2A
Hide Arm/Group Description Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity. Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
All-Cause Mortality
Bevacizumab + IFN-Alfa-2A Placebo + IFN-Alfa-2A
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Bevacizumab + IFN-Alfa-2A Placebo + IFN-Alfa-2A
Affected / at Risk (%) Affected / at Risk (%)
Total   103/337 (30.56%)   51/304 (16.78%) 
Blood and lymphatic system disorders     
Anaemia * 1  4/337 (1.19%)  5/304 (1.64%) 
Thrombocytopenia * 1  2/337 (0.59%)  0/304 (0.00%) 
Febrile neutropenia * 1  1/337 (0.30%)  0/304 (0.00%) 
Cardiac disorders     
Atrial fibrillation * 1  3/337 (0.89%)  1/304 (0.33%) 
Myocardial infarction * 1  1/337 (0.30%)  0/304 (0.00%) 
Congenital, familial and genetic disorders     
Hydrocele * 1  0/337 (0.00%)  1/304 (0.33%) 
Endocrine disorders     
Adrenal insufficiency * 1  0/337 (0.00%)  1/304 (0.33%) 
Hypercalcaemia of malignancy * 1  1/337 (0.30%)  0/304 (0.00%) 
Eye disorders     
Retinal vein thrombosis * 1  0/337 (0.00%)  1/304 (0.33%) 
Gastrointestinal disorders     
Abdominal pain * 1  3/337 (0.89%)  2/304 (0.66%) 
Diarrhoea * 1  2/337 (0.59%)  1/304 (0.33%) 
Constipation * 1  2/337 (0.59%)  0/304 (0.00%) 
Small intestinal haemorrhage * 1  2/337 (0.59%)  0/304 (0.00%) 
Small intestinal obstruction * 1  1/337 (0.30%)  1/304 (0.33%) 
Vomiting * 1  2/337 (0.59%)  0/304 (0.00%) 
Ascites * 1  1/337 (0.30%)  0/304 (0.00%) 
Colitis * 1  1/337 (0.30%)  0/304 (0.00%) 
Duodenal perforation * 1  1/337 (0.30%)  0/304 (0.00%) 
Gastric perforation * 1  1/337 (0.30%)  0/304 (0.00%) 
Gastric ulcer haemorrhage * 1  1/337 (0.30%)  0/304 (0.00%) 
Gastrointestinal haemorrhage * 1  1/337 (0.30%)  0/304 (0.00%) 
Gingival bleeding * 1  1/337 (0.30%)  0/304 (0.00%) 
Inguinal hernia * 1  1/337 (0.30%)  0/304 (0.00%) 
Intestinal perforation * 1  1/337 (0.30%)  0/304 (0.00%) 
Large intestine perforation * 1  1/337 (0.30%)  0/304 (0.00%) 
Nausea * 1  0/337 (0.00%)  1/304 (0.33%) 
Subileus * 1  1/337 (0.30%)  0/304 (0.00%) 
Intestinal ischaemia * 1  1/337 (0.30%)  0/304 (0.00%) 
General disorders     
Fatigue * 1  7/337 (2.08%)  0/304 (0.00%) 
Pyrexia * 1  5/337 (1.48%)  0/304 (0.00%) 
Asthenia * 1  2/337 (0.59%)  2/304 (0.66%) 
General physical health * 1  2/337 (0.59%)  0/304 (0.00%) 
Deterioration pain * 1  0/337 (0.00%)  2/304 (0.66%) 
Adverse drug reaction * 1  1/337 (0.30%)  0/304 (0.00%) 
Chills * 1  1/337 (0.30%)  0/304 (0.00%) 
Death * 1  0/337 (0.00%)  1/304 (0.33%) 
Injection site reaction * 1  1/337 (0.30%)  0/304 (0.00%) 
Malaise * 1  1/337 (0.30%)  0/304 (0.00%) 
Necrosis * 1  1/337 (0.30%)  0/304 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis * 1  1/337 (0.30%)  0/304 (0.00%) 
Hepatic failure * 1  1/337 (0.30%)  0/304 (0.00%) 
Jaundice * 1  1/337 (0.30%)  0/304 (0.00%) 
Infections and infestations     
Pneumonia * 1  8/337 (2.37%)  0/304 (0.00%) 
Gastroenteritis * 1  3/337 (0.89%)  1/304 (0.33%) 
Urinary tract infection * 1  2/337 (0.59%)  1/304 (0.33%) 
Lower respiratory tract infection * 1  0/337 (0.00%)  2/304 (0.66%) 
Infection anal abscess * 1  1/337 (0.30%)  0/304 (0.00%) 
Bronchopneumonia * 1  0/337 (0.00%)  1/304 (0.33%) 
Gastroenteritis salmonella * 1  0/337 (0.00%)  1/304 (0.33%) 
Hepatitis C * 1  0/337 (0.00%)  1/304 (0.33%) 
Infection * 1  1/337 (0.30%)  0/304 (0.00%) 
Labyrinthitis * 1  0/337 (0.00%)  1/304 (0.33%) 
Localised infection * 1  1/337 (0.30%)  0/304 (0.00%) 
Postoperative abscess * 1  1/337 (0.30%)  0/304 (0.00%) 
Rectal abscess * 1  1/337 (0.30%)  0/304 (0.00%) 
Renal abscess * 1  1/337 (0.30%)  0/304 (0.00%) 
Sepsis * 1  1/337 (0.30%)  0/304 (0.00%) 
Sinusitis * 1  1/337 (0.30%)  0/304 (0.00%) 
Staphylococcal sepsis * 1  1/337 (0.30%)  0/304 (0.00%) 
Urosepsis * 1  1/337 (0.30%)  0/304 (0.00%) 
Viral infection * 1  0/337 (0.00%)  1/304 (0.33%) 
Injury, poisoning and procedural complications     
Contusion * 1  0/337 (0.00%)  1/304 (0.33%) 
Medical device complication * 1  1/337 (0.30%)  0/304 (0.00%) 
Overdose * 1  0/337 (0.00%)  1/304 (0.33%) 
Postoperative wound * 1  1/337 (0.30%)  0/304 (0.00%) 
Complication traumatic haematoma * 1  1/337 (0.30%)  0/304 (0.00%) 
Upper limb fracture * 1  0/337 (0.00%)  1/304 (0.33%) 
Metabolism and nutrition disorders     
Hypercalcaemia * 1  3/337 (0.89%)  1/304 (0.33%) 
Dehydration * 1  2/337 (0.59%)  1/304 (0.33%) 
Cachexia * 1  1/337 (0.30%)  0/304 (0.00%) 
Diabetes mellitus * 1  0/337 (0.00%)  1/304 (0.33%) 
Hypoalbuminaemia * 1  0/337 (0.00%)  1/304 (0.33%) 
Hyponatraemia * 1  0/337 (0.00%)  1/304 (0.33%) 
Musculoskeletal and connective tissue disorders     
Pathological fracture * 1  1/337 (0.30%)  2/304 (0.66%) 
Back pain * 1  2/337 (0.59%)  0/304 (0.00%) 
Arthralgia * 1  1/337 (0.30%)  0/304 (0.00%) 
Chondrocalcinosis * 1  0/337 (0.00%)  1/304 (0.33%) 
Pyrophosphate muscular weakness * 1  1/337 (0.30%)  0/304 (0.00%) 
Musculoskeletal pain * 1  1/337 (0.30%)  0/304 (0.00%) 
Soft tissue necrosis * 1  1/337 (0.30%)  0/304 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Metastatic pain * 1  1/337 (0.30%)  1/304 (0.33%) 
Prostate cancer * 1  0/337 (0.00%)  2/304 (0.66%) 
Benign penile neoplasm * 1  1/337 (0.30%)  0/304 (0.00%) 
Rectal cancer * 1  1/337 (0.30%)  0/304 (0.00%) 
Squamous cell carcinoma of skin * 1  1/337 (0.30%)  0/304 (0.00%) 
Nervous system disorders     
Headache * 1  2/337 (0.59%)  1/304 (0.33%) 
Epilepsy * 1  1/337 (0.30%)  1/304 (0.33%) 
Syncope * 1  1/337 (0.30%)  1/304 (0.33%) 
Transient ischaemic attack * 1  2/337 (0.59%)  0/304 (0.00%) 
Cerebral ischaemia * 1  1/337 (0.30%)  0/304 (0.00%) 
Cerebrovascular accident * 1  1/337 (0.30%)  0/304 (0.00%) 
Encephalopathy * 1  1/337 (0.30%)  0/304 (0.00%) 
Gliosis * 1  1/337 (0.30%)  0/304 (0.00%) 
Haemorrhage intracranial * 1  0/337 (0.00%)  1/304 (0.33%) 
Hyperaesthesia * 1  1/337 (0.30%)  0/304 (0.00%) 
Lethargy * 1  0/337 (0.00%)  1/304 (0.33%) 
Leukoencephalopathy * 1  1/337 (0.30%)  0/304 (0.00%) 
Movement disorder * 1  0/337 (0.00%)  1/304 (0.33%) 
Nervous system disorder * 1  1/337 (0.30%)  0/304 (0.00%) 
Paraesthesia * 1  0/337 (0.00%)  1/304 (0.33%) 
Psychomotor hyperactivity * 1  1/337 (0.30%)  0/304 (0.00%) 
Somnolence * 1  0/337 (0.00%)  1/304 (0.33%) 
Spinal cord compression * 1  0/337 (0.00%)  1/304 (0.33%) 
Psychiatric disorders     
Confusional state * 1  3/337 (0.89%)  3/304 (0.99%) 
Depression * 1  4/337 (1.19%)  2/304 (0.66%) 
Anxiety * 1  1/337 (0.30%)  0/304 (0.00%) 
Mood altered * 1  1/337 (0.30%)  0/304 (0.00%) 
Renal and urinary disorders     
Haematuria * 1  1/337 (0.30%)  0/304 (0.00%) 
Hydronephrosis * 1  1/337 (0.30%)  0/304 (0.00%) 
Nephritic syndrome * 1  1/337 (0.30%)  0/304 (0.00%) 
Proteinuria * 1  1/337 (0.30%)  0/304 (0.00%) 
Renal failure * 1  0/337 (0.00%)  1/304 (0.33%) 
Renal failure acute * 1  0/337 (0.00%)  1/304 (0.33%) 
Renal impairment * 1  1/337 (0.30%)  0/304 (0.00%) 
Renal tubular necrosis * 1  0/337 (0.00%)  1/304 (0.33%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia * 1  0/337 (0.00%)  1/304 (0.33%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism * 1  5/337 (1.48%)  1/304 (0.33%) 
Epistaxis * 1  3/337 (0.89%)  0/304 (0.00%) 
Haemoptysis * 1  3/337 (0.89%)  0/304 (0.00%) 
Dyspnoea * 1  2/337 (0.59%)  0/304 (0.00%) 
Pneumothorax * 1  1/337 (0.30%)  1/304 (0.33%) 
Chronic obstructive pulmonary disease * 1  1/337 (0.30%)  0/304 (0.00%) 
Pleural effusion * 1  1/337 (0.30%)  0/304 (0.00%) 
Pneumonitis * 1  0/337 (0.00%)  1/304 (0.33%) 
Pulmonary congestion * 1  1/337 (0.30%)  0/304 (0.00%) 
Respiratory failure * 1  1/337 (0.30%)  0/304 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash * 1  2/337 (0.59%)  0/304 (0.00%) 
Eczema * 1  0/337 (0.00%)  1/304 (0.33%) 
Skin graft failure * 1  1/337 (0.30%)  0/304 (0.00%) 
Vascular disorders     
Hypertension * 1  3/337 (0.89%)  0/304 (0.00%) 
Hypotension * 1  0/337 (0.00%)  2/304 (0.66%) 
Aneurysm ruptured * 1  1/337 (0.30%)  0/304 (0.00%) 
Aortic aneurysm * 1  0/337 (0.00%)  1/304 (0.33%) 
Deep vein thrombosis * 1  1/337 (0.30%)  0/304 (0.00%) 
Hypertensive crisis * 1  1/337 (0.30%)  0/304 (0.00%) 
Venous thrombosis * 1  1/337 (0.30%)  0/304 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 11.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bevacizumab + IFN-Alfa-2A Placebo + IFN-Alfa-2A
Affected / at Risk (%) Affected / at Risk (%)
Total   319/337 (94.66%)   279/304 (91.78%) 
Blood and lymphatic system disorders     
Anaemia * 1  33/337 (9.79%)  39/304 (12.83%) 
Neutropenia * 1  23/337 (6.82%)  21/304 (6.91%) 
Thrombocytopenia * 1  21/337 (6.23%)  13/304 (4.28%) 
Gastrointestinal disorders     
Nausea * 1  97/337 (28.78%)  78/304 (25.66%) 
Diarrhoea * 1  70/337 (20.77%)  48/304 (15.79%) 
Vomiting * 1  47/337 (13.95%)  42/304 (13.82%) 
Constipation * 1  39/337 (11.57%)  25/304 (8.22%) 
Abdominal pain * 1  28/337 (8.31%)  25/304 (8.22%) 
Abdominal pain upper * 1  23/337 (6.82%)  13/304 (4.28%) 
Stomatitis * 1  17/337 (5.04%)  5/304 (1.64%) 
General disorders     
Pyrexia * 1  149/337 (44.21%)  130/304 (42.76%) 
Asthenia * 1  108/337 (32.05%)  83/304 (27.30%) 
Fatigue * 1  107/337 (31.75%)  83/304 (27.30%) 
Influenza like illness * 1  84/337 (24.93%)  78/304 (25.66%) 
Chills * 1  53/337 (15.73%)  54/304 (17.76%) 
Mucosal inflammation * 1  18/337 (5.34%)  11/304 (3.62%) 
Investigations     
Weight decreased * 1  68/337 (20.18%)  44/304 (14.47%) 
Metabolism and nutrition disorders     
Anorexia * 1  122/337 (36.20%)  93/304 (30.59%) 
Musculoskeletal and connective tissue disorders     
Myalgia * 1  63/337 (18.69%)  41/304 (13.49%) 
Arthralgia * 1  33/337 (9.79%)  28/304 (9.21%) 
Back pain * 1  38/337 (11.28%)  19/304 (6.25%) 
Pain in extremity * 1  26/337 (7.72%)  21/304 (6.91%) 
Bone pain * 1  23/337 (6.82%)  15/304 (4.93%) 
Musculoskeletal pain * 1  25/337 (7.42%)  13/304 (4.28%) 
Nervous system disorders     
Headache * 1  82/337 (24.33%)  50/304 (16.45%) 
Dizziness * 1  27/337 (8.01%)  27/304 (8.88%) 
Dysgeusia * 1  21/337 (6.23%)  13/304 (4.28%) 
Psychiatric disorders     
Depression * 1  38/337 (11.28%)  30/304 (9.87%) 
Insomnia * 1  21/337 (6.23%)  20/304 (6.58%) 
Anxiety * 1  9/337 (2.67%)  18/304 (5.92%) 
Renal and urinary disorders     
Proteinuria * 1  68/337 (20.18%)  9/304 (2.96%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis * 1  90/337 (26.71%)  11/304 (3.62%) 
Dyspnoea * 1  45/337 (13.35%)  38/304 (12.50%) 
Cough * 1  34/337 (10.09%)  39/304 (12.83%) 
Dysphonia * 1  17/337 (5.04%)  0/304 (0.00%) 
Skin and subcutaneous tissue disorders     
Dry skin * 1  32/337 (9.50%)  23/304 (7.57%) 
Pruritus * 1  30/337 (8.90%)  20/304 (6.58%) 
Alopecia * 1  24/337 (7.12%)  19/304 (6.25%) 
Rash * 1  17/337 (5.04%)  21/304 (6.91%) 
Vascular disorders     
Hypertension * 1  95/337 (28.19%)  27/304 (8.88%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 11.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor’s intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-LaRoche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00738530     History of Changes
Other Study ID Numbers: BO17705
2004-000282-35 ( EudraCT Number )
First Submitted: August 19, 2008
First Posted: August 20, 2008
Results First Submitted: March 22, 2016
Results First Posted: June 23, 2016
Last Update Posted: June 23, 2016